Various types of chemical sensors for detecting a chemical analyte and determining its concentration are known and are used in an ever growing variety of applications. Chemical sensors may for example be used to determine concentrations of compounds in industrial processes, to detect bio-agents that may contaminate air or water, and to monitor substances in the body of a patient that may be relevant to the patient's health. The sensors may be based on any of a large gamut of technologies, variations of the technologies, and combinations of the technologies. The technologies include optical, acoustic, photoacoustic, electromechanical, electromagnetic, and/or electronic technologies to note just a few of the technologies that are employed by chemical sensors to generate signals responsive to the presence and concentrations of chemical analytes.
For many applications it is advantageous for a chemical sensor to be small, robust, characterized by fast and accurate response to changes in concentration of an analyte, and of course, to be relatively inexpensive. For example, it may be advantageous for a chemical sensor, conventionally also referred to as a biochemical sensors, to be configured for use in or on the body of a patient for relatively extended periods of time to monitor body analytes that may be relevant for diagnosing the patient's health. To function satisfactorily, such a biochemical sensor, should generally be relatively immune to damage by body fluids, be responsive in real time to changes in concentrations of a body analyte for which it is intended to be responsive, and to be sufficiently small so that its presence in or on the body is neither damaging nor uncomfortably obtrusive. Among analytes whose concentrations may be of interest for monitoring as indicators of a patient's health are by way of example the concentrations of sodium and calcium ions, Na+ and Ca2+, and the concentration (pH) of hydrogen ions, H+.
Ion sensitive field effect transistors (ISFET), which were invented in 1970, are used to detect presence and concentrations of various species of ions, hereinafter target ions, in fluids into which they are placed. ISFETs have long been considered good candidates for providing small, fast, sensitive, accurate, and relatively inexpensive chemical and biochemical sensors. An ISFET typically comprises a reference electrode and a metal-oxide-semiconductor field effect transistor (MOSFET) modified to accumulate target ions the ISFET is intended to detect.
A conventional MOSFET comprises a source (S), a drain (D), and a conducting electrode referred to as a gate, formed in or on a semiconductor substrate, typically a silicon substrate. The source and drain may be n or p doped regions in the substrate, which is respectively p or n doped. The gate is formed generally from a metal or a polysilicon on a dielectric insulating layer, which overlies a region of the substrate between the source and the drain. The insulating layer is usually a layer of an oxide or nitride of the substrate material. A potential difference, “VGS”, applied between the gate and the substrate may be controlled to produce an electric field in the substrate that controls conductance of a conducting channel in a region, hereinafter referred to as a “channel region”, of the substrate between the drain and the source. For a given potential difference, “VDS”, between the drain and the source, the potential difference VGS may therefore be used to control magnitude of a current, “IDS,” driven by VDS between the drain and the source.
In an ISFET, the modified MOSFET comprises a source and drain formed in a substrate of the ISFET and a dielectric insulator on which a gate electrode in a conventional MOSFET is formed, but may be missing a gate electrode. The dielectric insulator in the ISFET may be left exposed and configured to preferentially accumulate target ions from among other ions that may be present in a fluid into which the ISFET is placed. Alternatively, the modified MOSFET may have a gate electrode but in addition have formed on the gate electrode a layer of material tailored to preferentially accumulate the target ions. Hereinafter, the material in an ISFET that accumulates target ions may be referred to as an accumulator.
In operation, when the ISFET is placed in a fluid to detect presence and concentration of target ion in the fluid, the accumulator is exposed to the fluid and the target ions so that a quantity of the target ions may be accumulated by the insulator. To generate signals responsive to the accumulated target ions that may be used to determine concentration of the target ions in the fluid, at least one power supply powers the ISFET to provide a voltage, VDS, between the drain and source of the ISFET's modified MOSFET and a voltage, “VRS”, between the reference electrode and the ISFET substrate. An electric field in the substrate that controls a current channel between the drain and source is a function of VRS and an electric field generated by a quantity of target ions from the fluid that may accumulate on the accumulator. For a given VRS, and a given VDS, current IDS in the ISFET is therefore a function of the quantity of target ions from the fluid that the accumulator accumulates.
Measurements of IDS or a known function of IDS, hereinafter generically referred to as measurements of IDS, are used to indicate the quantity of accumulated target ions. Under an assumption that the quantity of accumulated target ions is in dynamic equilibrium with, and changes in a known way with changes in concentration of target ions in the fluid, the measurements of IDS are used to estimate and track concentration of the target ions in the fluid. A measurements of IDS in a ISFET that is used to determine concentration of a target ion in a fluid may also be referred to hereinafter as a measurement of concentration, “ρT”, of the target ion.
Whereas, as noted above, ISFETs have long been expected to find popular use as small, robust, and accurate chemical and biochemical sensors, they do not appear to have satisfied the optimism of their expectations. In operation, ISFETs have too often proven to be relatively unstable and labile sensors that exhibit long and short term drifts in sensitivity and require calibration at frequencies that limit their utility. In addition, for many applications it has been difficult to satisfactorily protect ISFETs from damage by components of fluids in which they are used